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ABSTRACT: The usefulness of anticoagulation in patients with suspected non-massive pulmonary embolism (PE) is uncertain. We recently published a decision analysis model suggesting a benefit for preemptive anticoagulation in patients with an intermediate or high probability of PE, even with short diagnostic delays (0-3 h). In case of a low probability of PE, the decision to treat or not could partly rely on the expected diagnostic delay. Once the diagnosis is confirmed, achieving rapidly therapeutic anticoagulation levels decreases future thrombotic complications.
Revue médicale suisse 02/2013; 9(372):306-8, 310.
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ABSTRACT: Cancer is a known risk factor for the development of venous thromboembolism (VTE) and in particular, adenocarcinoma of the lung is known to be associated with a higher risk of thromboembolic event. EGFR activating mutations are more frequently found in this histological subtype than in other lung cancers. We report three cases of VTE in patients with adenocarcinoma of the lung and EGFR activating mutation. Our reported case series is atypical because the VTE event occurred early in the adenocarcinoma history: either leading to the diagnosis of cancer, or appearing very early in the management of the neoplasm.
Revue des Maladies Respiratoires 11/2012; 29(9):1137-40. · 0.59 Impact Factor
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ABSTRACT: Venous thromboembolism (VTE), comprising deep vein thrombosis and pulmonary embolism, is a common potentially lethal condition [1-2]. Treatment with oral anticoagulation (OAC) therapy is effective at reducing recurrent VTE, but long-term oral anticoagulation therapy needs to be counterbalanced with the risk of major bleeding. Identification of subgroups of patients with unprovoked VTE that have lower and higher risk of recurrent VTE is important to help tailor length of anticoagulation in this population. © 2012 International Society on Thrombosis and Haemostasis.
Journal of Thrombosis and Haemostasis 10/2012; · 5.73 Impact Factor
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R S Chitsike,
M A Rodger,
M J Kovacs,
M T Betancourt,
P S Wells,
D R Anderson,
I Chagnon, G LE Gal,
S Solymoss,
M A Crowther,
A Perrier,
R H White,
L M Vickars,
T Ramsay,
S R Kahn
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ABSTRACT: Background: Risk factors for post-thrombotic syndrome (PTS) remain poorly understood. Objectives: In this multinational multicenter study, we evaluated whether subtherapeutic warfarin anticoagulation was associated with the development of PTS. Methods: Patients with a first unprovoked deep venous thrombosis (DVT) received standard anticoagulation for 5-7 months and were then assessed for PTS. The time in the therapeutic range was calculated from the international normalized ratio (INR) data. An INR below 2, more than 20% of the time, was considered as subtherapeutic anticoagulation. Results: Of the 349 patients enrolled, 97 (28%) developed PTS. The overall frequency of PTS in patients with subtherapeutic anticoagulation was 33.5%, compared with 21.6% in those with an INR below two for ≤ 20% of the time (P = 0.01). During the first 3 months of therapy, the odds ratio (OR) for developing PTS if a patient had subtherapeutic anticoagulation was 1.78 (95% confidence interval [CI] 1.10-2.87). After adjusting for confounding variables, the OR was 1.84 (95% CI 1.13-3.01). Corresponding ORs for the full period of anticoagulation were 1.83 (95% CI 1.14-3.00) [crude] and 1.88 (95% CI 1.15-3.07) [adjusted]. Conclusion: Subtherapeutic warfarin anticoagulation after a first unprovoked DVT was significantly associated with the development of PTS.
Journal of Thrombosis and Haemostasis 07/2012; 10(10):2039-2044. · 5.73 Impact Factor
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ABSTRACT: The introduction of computed tomography pulmonary angiography (CTPA) has led to an increase in the incidence of pulmonary embolism (PE) diagnosis. However, the case fatality rate is lower and the mortality rates of PE have remained unchanged, suggesting a lower severity of illness. Specifically, the multiple-detector CTPA increased the rate of subsegmental filling defect reported in patients with suspected PE. Whether these filling defects reported on CTPA would correlate with true subsegmental PE (SSPE) on pulmonary angiography or are actually artifacts is unknown. The inter-observer agreement for SSPE diagnosis among radiologists with varied levels of experience is low (κ of 0.38; 95% CI, 0.0-0.89). Furthermore, the clinical importance of a symptomatic SSPE diagnosed by CTPA is unclear. SSPE are frequent on pulmonary angiography in patients with a low probability ventilation-perfusion (V/Q) scan for suspected PE. Several prospective management cohort studies have demonstrated that patients with low or intermediate V/Q scan results can be safely managed without anticoagulation by combining the scan results with the pretest probability (PTP) of PE and compression ultrasonography. Although clinical equipoise exists, the majority of patients diagnosed with SSPE on CTPA are currently treated with anticoagulant therapy. Only a small number of patients with SSPE diagnosed by CTPA and without DVT who did not receive anticoagulation treatment have been reported in the literature. None of these patients suffered recurrent symptomatic VTE (PE or DVT) during the 3-month follow-up period (0%; 95% CI, 0-7.4%), suggesting that SSPE might be clinically unimportant. These conclusions are only hypothesis generating and need to be confirmed in prospective clinical management studies before changing clinical practice.
Journal of Thrombosis and Haemostasis 06/2012; 10(8):1486-90. · 5.73 Impact Factor
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J-P Galanaud,
C A Holcroft,
M A Rodger,
M J Kovacs,
M T Betancourt,
P S Wells,
D R Anderson,
I Chagnon, G Le Gal,
S Solymoss,
M A Crowther,
A Perrier,
R H White,
L M Vickars,
T Ramsay,
S R Kahn
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ABSTRACT: Post-thrombotic syndrome (PTS) is the most frequent complication of a deep vein thrombosis (DVT). International guidelines recommend assessing PTS with the Villalta scale, a clinical measure that incorporates venous symptoms and signs in the leg ipsilateral to a DVT. However, these signs and symptoms are not specific for PTS and their prevalence and relevance in the contralateral leg have not previously been studied.
Using data from the REVERSE prospective multicentre cohort study, we compared the Villalta total score and prevalence of venous signs and symptoms in the ipsilateral vs. contralateral leg in patients with a first, unilateral DVT 5 to 7 months previously.
Among the 367 patients analyzed, the mean Villalta score was higher in the ipsilateral than in the contralateral leg (mean ± standard deviation [SD] 3.7 [3.4] vs. 1.9 [2.5], respectively; P<0.0001). Villalta scores in the ipsilateral and contralateral legs were strongly correlated (r=0.68; P<0.0001). Ipsilateral PTS (defined by a Villalta total score >4) was present in 31.6% (n=116) of patients. Among these, 39.7% (n=46) of patients had a Villalta score >4 in the contralateral leg, and the distribution of Villalta symptoms and signs components was similar between the legs.
Villalta scores in the ipsilateral and contralateral legs are strongly correlated. Almost half of cases considered to be PTS might reflect pre-existing symptomatic chronic venous disease. Alternatively, patients with pre-existing chronic venous disease might be more prone to developing PTS after a DVT. Performing a bilateral assessment of Villalta scores at the acute phase of DVT could be of clinical interest from a diagnostic, prognostic and therapeutic point of view.
Journal of Thrombosis and Haemostasis 06/2012; 10(6):1036-42. · 5.73 Impact Factor
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ABSTRACT: Age-adjusted D-dimer cut-off has recently been proposed to increase D-dimer usefulness in older patients suspected of pulmonary embolism (PE).
We externally validated this age-adjusted D-dimer cut-off using different D-dimer assays in a multicenter sample of emergency department patients.
Secondary analysis of three prospectively collected databases (two European, one American) of patients suspected of having PE. D-dimer performance for ruling out PE was assessed by calculating negative likelihood ratio (nLR) for D-dimer with age-adjusted D-dimer cut-off (< age × 10 in patients over 50 years) and with conventional cut-off (< 500 μg dL(-1)). Test efficiency was assessed by the number needed to test (NNT) to rule out PE in one patient.
Among 4537 patients included, overall PE prevalence was 10.1%. In the overall population, nLR was 0.06 (95% confidence interval, 0.03-0.09) with conventional cut-off and 0.08 (0.05-0.12) with age-adjusted cut-off. Using age-adjusted cut-off, nLR was 0.08, 0.09 and 0.06 for Vidas(®) , Liatest(®) and MDA(®) assays, respectively. Use of age-adjusted cut-off produced a favorable effect on NNT in the elderly; the greatest decrease was observed in patients > 75 years: NTT halved from 8.1 to 3.6. The proportion of patients over 75 years with normal D-dimer was doubled (27.9% vs. 12.3%).
Our study shows that age-adjusted D-dimer had low nLR, allowing its use as a rule-out PE strategy in non-high pretest clinical probability patients, as well as using Vidas(®), Liatest(®) or MDA(®) assays. This age-adjusted cut-off increased clinical usefulness of D-dimer in older patients. A large prospective study is required to confirm these results.
Journal of Thrombosis and Haemostasis 05/2012; 10(7):1291-6. · 5.73 Impact Factor
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ABSTRACT: Septic thrombophlebitis on a central venous access device (CVAD) is a rare and serious complication. According to current guidelines, the device should be removed and antibiotics be given. The risk of septic thrombophlebitis is related to the migration of septic emboli to the lung, a potentially fatal event, particularly in frail patients with lung cancer. We report a case observed in a 66-year-old man with multiple metastatic lung cancer who had a CVAD and who developed septic thrombophlebitis leading to coagulase-negative staphylococcal bacteriemia. After removal of the CVAD, the thrombophlebitis was complicated by pulmonary embolism affecting the entire network of the right lung.
Journal des Maladies Vasculaires 04/2012; 37(3):146-9. · 0.54 Impact Factor
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ABSTRACT: Venous thromboembolism (VTE) is a common disease. The incidence rises markedly with increasing age; over the age of 75, the annual incidence reaches 1 per 100.
Besides major risk factors (surgery, trauma and acute medical illness), four risk factors have to be taken into account in the management of VTE: increasing age, cancer, previous history of VTE and pregnancy. To date, with the exception of the antiphospholipid syndrome and antithrombin deficiency, "thrombophilias" do not appear to change the management of VTE.
"Thrombophilias" are useful tools for understanding the pathophysiology of VTE. Therefore, further studies are needed to identify new biological anomalies and their impact on the risk of VTE. Recently, links between VTE and atherosclerosis have been demonstrated, leading to new concept of pan-vascular disease and prevention.
VTE is a major public health problem. The knowledge of VTE risk factors is of major importance in identifying high-risk patients and in reducing the incidence and mortality of VTE.
Revue des Maladies Respiratoires 02/2012; 29(2):254-66. · 0.59 Impact Factor
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ABSTRACT: Patients with suspected deep vein thrombosis (DVT) are often managed on an outpatient basis. The aim of the study was to validate a clinical prediction rule specifically for use in primary care to help physicians in their decision to start anticoagulant therapy while awaiting ultrasound examination.
Between September 2007 and October 2008, 194 general practitioners prospectively included patients with clinically suspected DVT without clinically suspected pulmonary embolism. All patients underwent a standardized clinical assessment in order to collect items included in the clinical prediction rule (personal history of venous thromboembolism +1, immobilization in previous month+1, estrogen contraceptive+2, active malignancy+3, swelling of the calf+1, the presence of an alternative diagnosis more likely than that of DVT-3. DVT unlikely if score<2, likely if score≥2).
Among the 164 included patients, 56 (34%) had DVT of them 28 (17%) had a proximal DVT. Proportions of confirmed DVT were 29% in the unlikely group and 43% in the likely group against 26% and 63% respectively in the derivation study.
This clinical prediction rule might not fulfill the required conditions to be considered as a usable help in the ambulatory management of DVT. Variations of the cut-off value could enhance its performance.
La Revue de Médecine Interne 01/2012; 33(5):244-9. · 0.61 Impact Factor
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Journal of Thrombosis and Haemostasis 12/2011; 10(3):496-8. · 5.73 Impact Factor
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G Gex,
E Gerstel,
M Righini, G LE Gal,
D Aujesky,
P-M Roy,
O Sanchez,
F Verschuren,
O T Rutschmann,
T Perneger,
A Perrier
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ABSTRACT: A pulmonary embolism (PE) is thought to be associated with atrial fibrillation (AF). Nevertheless, this association is based on weak data.
To assess whether the presence of AF influences the clinical probability of PE in a cohort of patients with suspected PE and to confirm the association between PE and AF.
We retrospectively analyzed the data from two trials that included 2449 consecutive patients admitted for a clinically suspected PE. An electrocardiography (ECG) was systematically performed and a PE was diagnosed by computer tomography (CT). The prevalence of AF among patients with or without a PE was compared in a multivariate logistic regression model.
The prevalence of PE was 22.8% (519/2272) in patients without AF and 18.8% (25/133) in patients with AF (P = 0.28). After adjustment for confounding factors, AF did not significantly modify the probability of PE (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.42-1.11). However, when PE suspicion was based on new-onset dyspnea, AF significantly decreased the probability of PE (OR 0.47, 95% CI 0.26-0.84). If isolated chest pain without dyspnea was the presenting complaint, AF tended to increase the probability of PE (OR 2.42, 95% CI 0.97-6.07).
Overall, the presence of AF does not increase the probability of PE when this diagnosis is suspected. Nevertheless, when PE suspicion is based on new-onset dyspnea, AF significantly decreases the probability of PE, as AF may mimic its clinical presentation. However, in patients with chest pain alone, AF tends to increase PE probability.
Journal of Thrombosis and Haemostasis 12/2011; 10(3):347-51. · 5.73 Impact Factor
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ABSTRACT: Suspected deep vein thrombosis (DVT) of lower limbs (LL) may require different tools to rule out or confirm the diagnosis. Clinical probability provides help to select useful tests, interpret their results, and decide to treat the patient meanwhile. Clinical prediction rules that risk stratify patients with suspected DVT can be established from inpatients, but no prediction rule not requiring laboratory tests has been established from primary care patients. We previously derived and internally validated such a prediction rule. The aim of this study is to externally validate this score.
The score was applied to Optimev outpatients with suspected LL-DVT, and without suspected pulmonary embolism. Sensitivity and specificity were calculated for proximal and distal DVT, according to each score. The area under the ROC curve was calculated for each kind of DVT, in order to assess the validity of the score on predicting the presence or absence of DVT.
Among 3523 outpatients prospectively included in the Optimev study for suspected LL DVT, overall prevalence of DVT was 29.7% (n=1046), ranging from 21.7% in the non-high score probability, to 61.4% in the high score probability. The area under the ROC curve was 0.79 [CI 95%, 0.77-0.80]. With subgroup analysis, the area under curve was 0.83 [CI 95%, 0.82-0.85] for proximal DVT, and 0.75 [CI 95%, 0.73-0.77] for distal DVT.
This score reliably identifies primary care patients with LL DVT, whether proximal or distal.
Journal des Maladies Vasculaires 12/2011; 37(1):9-14. · 0.54 Impact Factor
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ABSTRACT: After a first unprovoked venous thromboembolism (VTE), many patients have residual pulmonary and/or lower limb vascular obstruction following completion of short-term anticoagulation. Residual vascular obstruction may complicate the diagnosis of recurrent VTE. Whether baseline imaging, conducted after completion of anticoagulation, helps in interpreting diagnostic testing in patients who subsequently have suspected recurrent VTE is unknown.
The REVERSE study is a cohort study whose primary aim was to derive a clinical decision rule to guide the duration of anticoagulation after a first unprovoked VTE. All patients underwent baseline imaging after completing 5-7 months of anticoagulant therapy. We performed a post hoc randomized controlled comparison among 121 patients investigated for a suspected recurrent VTE during follow-up: the decision on recurrent VTE with or without baseline imaging was made available to two independent adjudicators.
The proportion of patients not classifiable for recurrent VTE was statistically significantly higher in the group with no baseline imaging than in the group with baseline imaging: one in five as compared with one in 25. The interobserver agreement between the two adjudicators was better in the group with baseline imaging than in the group with no baseline imaging: κ-values were 0.78 and 0.54, respectively.
In patients with a first unprovoked VTE, baseline imaging at completion of anticoagulant therapy helps in interpreting diagnostic tests performed in cases of suspected recurrent VTE.
Journal of Thrombosis and Haemostasis 12/2011; 9(12):2406-10. · 5.73 Impact Factor
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La Revue de Médecine Interne 12/2011; 32 Suppl 2:S236-40. · 0.61 Impact Factor
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ABSTRACT: Genetic variants of the enzyme that metabolizes warfarin, cytochrome P-450 2C9 (CYP2C9) and of a key pharmacologic target of vitamin K antagonists, vitamin K epoxide reductase (VKORC1), contribute to differences in patients' responses to coumarin derivatives. The role of these variants in fluindione response is unknown. Our aim was to assess whether genetic factors contribute to the variability in the response to fluindione.
Four hundred sixty-five patients with a venous thromboembolic event treated by fluindione for at least 3 months with a target international normalized ratio (INR) of 2.0 to 3.0 were studied. VKORC1, CYP2C9, CYP4F2 and EPHX1 genotypes were assessed. INR checks, fluindione doses and bleeding events were collected.
VKORC1 genotype had a significant impact on early anticoagulation (INR value ≥2 after the first two intakes) (P < 0.0001), on the time required to reach a first INR within the therapeutic range (P < 0.0001) and on the time to obtain a first INR value > 4 (P= 0.0002). The average daily dose of fluindione during the first period of stability was significantly associated with the VKORC1 genotype: 19.8 mg (±5.5) for VKORC1 CC, 14.7mg (±6.2) for VKORC1 CT and 8.2mg (±2.5) for VKORC1 TT (P < 0.0001). CYP2C9, CYP4F2 and EPHX1 genotypes did not significantly influence the response to fluindione.
VKORC1 genotype strongly affected anticoagulation induced by fluindione whereas CYP2C9, CYP4F2 and EPHX1 genotypes seemed less determining.
British Journal of Clinical Pharmacology 08/2011; 73(3):428-36. · 2.96 Impact Factor
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Journal of Thrombosis and Haemostasis 08/2011; 9(10):2115-7. · 5.73 Impact Factor
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Journal of Thrombosis and Haemostasis 04/2011; 9(7):1412-5. · 5.73 Impact Factor
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ABSTRACT:
Residual vein obstruction (RVO) detected on compression ultrasonography of the leg after a few months of anticoagulation therapy might be able to identify patients with deep vein thrombosis (DVT) at high risk of having a recurrent venous thromboembolism (VTE). Aim: To determine whether RVO is associated with an increased risk of recurrent events in patients with DVT.
A systematic literature search strategy was conducted using MEDLINE, EMBASE, and the Cochrane Register of Controlled Trials. We selected 14 articles (nine prospective cohort studies and five randomized controlled trials) that included patients with DVT who had an assessment for RVO with the use of compression ultrasonography. Two reviewers independently extracted data onto standardized forms.
Overall, the presence of RVO was not associated with an increased risk of recurrent VTE (odds ratio [OR] 1.24, 95% confidence interval [CI] 0.9-1.7) in patients with unprovoked DVT who stopped oral anticoagulation therapy at the time of RVO assessment. However, RVO was significantly associated with recurrent VTE in patients with any (unprovoked or provoked) DVT (OR 1.5, 95% CI 1.1-2.0).
RVO was associated with a modestly increased risk of recurrent VTE in patients with DVT (unprovoked and provoked). However, RVO did not seem to be a predictor of recurrent VTE in patients with unprovoked DVT following anticoagulation discontinuation. Further prospective studies are needed to assess the role of RVO in patients with unprovoked DVT.
Journal of Thrombosis and Haemostasis 03/2011; 9(6):1119-25. · 5.73 Impact Factor
